Abstract
BackgroundCell division cycle-associated (CDCA) gene family is essential to cell cycle regulation. Numerous studies have illuminated that dysfunction of CDCA genes may not only lead to uncontrolled cell proliferation resulting in tumorigenesis but also influence immune cell infiltration in tumors. However, the role of the CDCA gene family on the prognosis and immune infiltration in nasopharyngeal carcinoma (NPC) remains to be unclear.MethodsSBC human ceRNA array V1.0 was used to measure mRNA expression in three pairs of NPC tissues and nasopharyngitis tissues. The expression of CDCA8 was confirmed in an IHC microarray containing 130 NPC patients. Two external GEO cohorts were enrolled for further analysis. Prognosis analysis was performed using the Kaplan–Meier method. Gene set enrichment analysis (GSEA) was applied to explore the potential mechanism of CDCA genes in NPC. The relationship between CDCA gene family and immune infiltration in NPC was evaluated using the Xcell tool.ResultsCDCA genes were broadly upregulated in NPC tissues compared to nasopharyngitis tissues, and high expression of CDCA3/5/8 indicated worse prognosis in NPC. Besides cell cycle pathways, we found that CDCA3/5/8 were involved in multiple immune-related pathways. Overexpression of CDCA8 was strongly associated with less infiltration of CD8+ T cells and more infiltration of CD4+ Th1 cells and was negatively correlated with immune checkpoint blockade (ICB)-related genes.ConclusionCDCA gene family was upregulated in NPC, and their expressions were associated with adverse prognosis. High expression of CDCA8 was associated not only with poor prognosis, but also with less immune infiltration and downregulation of ICB-related genes in NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma arising from the epithelial lining of the nasopharynx with a specific geographic distribution
Three members of the Cell division cycle-associated (CDCA) gene family, Cell division cycleassociated protein 2 (CDCA2) (FC = 2.21, p = 0.038), Cell division cycle-associated protein 5 (CDCA5) (FC = 3.10, p = 0.036), and Cell division cycleassociated protein 8 (CDCA8) (FC =2.17, p = 0.039), were found to be upregulated in NPC tissues compared with the NE tissues (Figure 1A, Supplementary Table 1)
The expression of Cell division cycleassociated protein 1 (CDCA1)/2/4/6/7/8 was higher in NPC tissues than in nasopharyngitis tissues (Figure 1B, all p < 0.001)
Summary
Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma arising from the epithelial lining of the nasopharynx with a specific geographic distribution. 70% of newly diagnosed NPC patients are at advanced stages. Intensity-modulated radiation therapy (IMRT) is the recommended therapy for advanced NPC patients [3], but patients are more likely to suffer treatment failure from radiotherapy due to radioresistance, which is the leading cause of NPC mortality [4]. NPC patients in the late stages treating with IMRT usually suffer from severe treatment-related complications that reduce the quality of life [5]. Cell division cycle-associated (CDCA) gene family is essential to cell cycle regulation. Numerous studies have illuminated that dysfunction of CDCA genes may lead to uncontrolled cell proliferation resulting in tumorigenesis and influence immune cell infiltration in tumors. The role of the CDCA gene family on the prognosis and immune infiltration in nasopharyngeal carcinoma (NPC) remains to be unclear
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